Background: Glioblastomas (GBM) are one of the most aggressive tumor of the central nervous system with an average life expectancy of only 1-2 years after diagnosis, even with the use of advanced treatments with surgery, radiation, and chemotherapy. There are several anticancer drugs with alkylating properties that have been used in the therapy of malignant gliomas. Temozolomide (TMZ) is one of them, widely used even in combination with ionizing radiation. However, the main disadvantage of using these types of drugs in the treatment of GBM is the development of cancer drug resistance. Research of bioactive compounds with anticancer activity has been heavily explored. Purpose: This review focuses on a carotenoid and a phlorotannin present in seaweed, namely fucoxanthin and phloroglucinol, and their anticancer activity against glioblastoma. The combination of natural compounds with conventional drugs is also discussed. Conclusion: Several natural compounds existing in seaweeds, such as fucoxanthin and phoroglucinol, have shown cytotoxic activity in models in vitro and in vivo, acting through different molecular mechanisms, such as antioxidant, antiproliferative, DNA damage/DNA repair, proapoptotic, antiangiogenic and antimetastic. Within the scope of interactions with conventional drugs, there are evidences that some seaweed compounds could be used to potentiate the action of anticancer drugs. However, their effects and mechanisms of action, alone or in combination with anticancer drugs, namely TMZ, in glioblastoma cell, still few explored and require more attention due to the unquestionable high potential of these marine compounds.